Estrogen Receptor Expression in Prostate Cancer and Premalignant Prostatic Lesions

Bonkhoff, Helmut; Fixemer, Thomas; Hunsicker, Isabel; Remberger, K.

doi:10.1016/s0002-9440(10)65160-7

Cited by 211 publications

(222 citation statements)

References 35 publications

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“…Another mode of RAC 3 activity in prostate cancer cells may be via its well characterised interaction with the ER (Anzick et al, 1997;Tikkanen et al, 2000;Xu et al, 2000). The oestrogen receptor (ER) has been shown to be present in human prostate cancer and pre-malignant lesions (Bonkhoff et al, 1999), while the prostate cell lines LNCaP, DU 145 and PC 3 have been shown to express the β isoform of the receptor (Lau et al, 2000). From these studies, ER status appears to be an important factor in prostate cancer progression.…”

Section: Discussionmentioning

confidence: 99%

Expression of RAC 3, a steroid hormone receptor co-activator in prostate cancer

et al. 2001

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RAC 3, one of the p160 family of co-activators is known to enhance the transcriptional activity of a number of steroid receptors. As co-activators are also known to enhance androgen receptor (AR) activity, we investigated the role of RAC 3 in the context of prostate cancer. In prostate cancer cell lines, we found variable levels of the RAC 3 protein with highest expression seen in AR-positive LNCaP cells, moderate expression in AR-negative PC 3 cells and low-level expression in AR-negative DU 145 cells. Immuno-precipitation studies showed that endogenous RAC 3 interacted with the AR in vivo and transfection assays confirmed that RAC 3 enhanced AR transcriptional activity. In clinical prostate tissue, we found strong RAC 3 mRNA expression and immuno-histochemistry demonstrated that in benign tissue, the protein was expressed predominantly in luminal cells, while in primary malignant epithelium it was more homogeneously expressed. In a series of 37 patients, the levels of RAC 3 expression correlated significantly with tumour grade ( P = 0.01) and stage of disease ( P = 0.03) but not with serum PSA levels. In addition moderate or high RAC 3 expression was associated with poorer disease-specific survival ( P = 0.03). We conclude that RAC 3 is an important co-activator of the AR in the prostate and may have an important role in the progression of prostate cancer. © 2001 Cancer Research Campaign http://www.bjcancer.com

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Section: Discussionmentioning

confidence: 99%

Expression of RAC 3, a steroid hormone receptor co-activator in prostate cancer

et al. 2001

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“…Thus it was proposed that ERα may have a tumor suppressor role in the prostate gland and loss of its expression may be an early event in prostatic disease. Interestingly, ERα expression has been observed in some prostate cancer cell lines [86] as well as in hormone refractory and metastatic lesions suggesting its re-emergence as cancer progresses [87] although this has not been consistently seen in all studies [88]. It is also noteworthy that prostate cancer risk has been associated with genetic polymorphisms in the ERα gene particularly within Japanese and African American populations implicating a potential causal relationship between ERα mediated estrogenic action and prostate cancer [89,90].…”

Section: Erαmentioning

confidence: 99%

The role of estrogens and estrogen receptors in normal prostate growth and disease

2008

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Keywordsprostate; prostate cancer; estrogens; estradiol; estrogen receptor Estrogens have significant direct and indirect effects on prostate gland development and homeostasis and have been long suspected in playing a role in the etiology of prostatic diseases. Direct effects are mediated through prostatic estrogen receptors alpha (ERα) and beta (ERβ) with expression levels changing over time and with disease progression. The present review examines the evidence for a role of estrogens and specific estrogen receptors in prostate growth, differentiation and disease states including prostatitis, benign prostatic hyperplasia (BPH) and cancer and discusses potential therapeutic strategies for growth regulation via these pathways. Estrogens in the Male and Effects on the Prostate GlandWhile low levels of circulating estrogens are present throughout life in males, there are two time periods, during in utero development and aging, when males are exposed to relatively higher levels of circulating estradiol which have been shown to impact the prostate gland. In addition, estrogens may be produced locally within the prostate via conversion of testosterone to 17β-estradiol by aromatase expressed within the prostate stroma [1,2], thus estrogen action in the prostate may occur independent of serum levels of this steroid.During the third trimester of in utero development in humans, rising maternal estradiol and declining fetal androgen production result in an elevated estrogen/testosterone (E/T) ratio. This relative increase in estradiol has been shown to directly stimulate extensive squamous metaplasia within the developing prostatic epithelium which regresses immediately after birth when estrogen levels rapidly decline [3,4]. Although the natural role for estrogens during prostatic development is unclear, it has been proposed that excessive estrogenization during prostatic development may contribute to the high incidence of BPH and prostatic carcinoma currently observed in the aging male population [5]. African-American men have a two-fold increased risk of prostatic carcinoma as compared to their Caucasian counterparts and it has been suggested that this is related, in part, to elevated levels of maternal estrogens during early gestation in this population [6,7]. Indicators of pregnancy estrogen levels such as length of Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers

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“…130 Prostate-specific membrane antigen, an abundant transmembrane glycoprotein, shows increased expression in PIN and cancer when compared with benign epithelium, 131,132 and this expression was unaffected by short-term androgen deprivation therapy. 132 Estrogen receptor alpha is present in up to 28% of cases of PIN and 43% of cancers, but estrogen receptor beta is absent; 133 prolactin receptor expression is increased in PIN. 134 A model of prostatic carcinogenesis has been proposed based on the morphologic continuum of PIN and the multistep theory of carcinogenesis.…”

Section: Genetic and Molecular Changesmentioning

confidence: 99%

High-grade prostatic intraepithelial neoplasia

2004

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High-grade prostatic intraepithelial neoplasia (PIN) is now accepted as the most likely preinvasive stage of adenocarcinoma, almost two decades after its first formal description. PIN has a high predictive value as a marker for adenocarcinoma, and its identification warrants repeat biopsy for concurrent or subsequent invasive carcinoma. The only method of detection is biopsy; PIN does not significantly elevate serum prostate-specific antigen (PSA) concentration or its derivatives and cannot be detected by current imaging techniques, including ultrasound. Most patients with PIN will develop carcinoma within 10 years. PIN is associated with progressive abnormalities of phenotype and genotype, which are similar to cancer rather than normal prostatic epithelium, indicating impairment of cell differentiation with advancing stages of prostatic carcinogenesis. Androgen deprivation therapy decreases the prevalence and extent of PIN, suggesting that this form of treatment may play a role in chemoprevention.

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Estrogen Receptor Expression in Prostate Cancer and Premalignant Prostatic Lesions

Cited by 211 publications

References 35 publications

Expression of RAC 3, a steroid hormone receptor co-activator in prostate cancer

Expression of RAC 3, a steroid hormone receptor co-activator in prostate cancer

The role of estrogens and estrogen receptors in normal prostate growth and disease

High-grade prostatic intraepithelial neoplasia

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